The purpose of this Program Project is to develop an understanding of the epidemiology, natural history and pathogenesis of maternal and congenital CMV infection that will serve as a foundation for efforts to prevent congenital CMV infection. cytomegalovirus is the leading infectious cause of brain disease in children in the United States. there are approximately 40,000 cases of congenital CMV infection in the U.S. each year; around 8,000 of these will develop some degree of CNS handicaps. Sequelae of congenital CMV infection include sensorineural hearing loss, cerebral palsy and mental retardation. Planning an approach to prevention of maternal gestational and fetal CMV infections has been stymied by the discovery in the 1970's that maternal immunity did not prevent transmission of virus to the fetus. Project 1, Maternal CMV Infection in Two Populations, will identify congenital CMV infections by screening of newborns in two populations: a University Hospital obstetric service that is a predominantly black. low income population and a private obstetric practice that is a predominantly white, middle income group. Results to date have shown that congenital CMV infection is far more common in the low income group with a rate of 12/1000 births compared with the rate of 4/1000 births in the middle income group. Project 1 will also categorize type of maternal infection (primary vs recurrent) through use of serologic tests on prenatal and preconceptional sera, and in primary infections, define the gestational age at maternal infection. Project 2, Outcome of Congenital CMV Infection, is a follow- up study of children with congenital CMV infection; it will determine rates of sequelae in children in the various categories defined by maternal infection and clarify the importance of silent congenital CMV infection as a cause of mental retardation. Project 3, Adolescent Pregnancy and Congenital CMV Infection, is a cohort study in a teen maternity clinic that has had an extraordinarily high rate of maternal infection and congenital infection (7%) in babies. This project will identify risk factors for maternal infection and congenital infection in babies. It will also use restriction endonuclease analysis of CMV strains to seek evidence of reinfection or reactivation of virus. Project 4, Pathogenesis of Congenital HCMV Infections, is a study of the pathogenesis of maternal and infant CMV infection that will examine the role of antibody and lymphocyte responses to specific viral proteins in preventing transmission or damage from infection.